Organotin-mediated monoacylation of diols with reversed chemoselectivity. Mechanism and selectivity

The monoesterification of unsymmetrically substituted diols, which occurs at the most substituted hydroxyl when activation of the substrate is achieved through its dibutylstannylene acetal, has been investigated to ascertain the origin of the unusual reversal of chemoselectivity. A mechanism in which the dibutylstannylene acetal plays the double role of reagent and catalyst has been established, which accounts for the reactivity, selectivity, and product distribution of the reaction, The reaction pathway involves three subsequent steps, namely, (a) esterification, (b) intra- and intermolecular transesterification, and (c) quench; interplay between kinetic and thermodynamic control over the three steps is responsible for the observed product distribution. The knowledge of the reaction mechanism allows for adjustment of experimental conditions to achieve optimum selectivity, which can be >99% with the appropriate choice of reagents. The stannylation procedure converts hydroxyls into functional groups highly chemoselective toward acyl reagents, but inert toward sulfonyl halides and alkylating reagents. The reactivity of the Sn-O bond has been found to decrease with decreasing the electronegativity of ligands on tin, while halide ligands appear to be essential for reversal of chemoselectivity. A structure has been proposed for the catalytic species, in which complexation of the stannyl monoester intermediates with the starting dioxastannolane reagent activates the stannylated oxygen toward addition to the carbonyl and at the same time accounts for the steric hindrance that biases the intramolecular transesterification equilibrium toward the thermodynamically most stable monoester of the most substituted hydroxyl.